CFTR expression decreases with age in several airway cell types

Area of Science:

• Pulmonary Medicine
• Molecular Biology
• Aging Research

Background:

• The mucociliary clearance (MC) system is crucial for lung defense against pathogens.
• MC efficiency relies on ciliary function and airway surface liquid (ASL) hydration.
• Age-related decline in MC is linked to increased pulmonary infection rates in older adults.

Purpose of the Study:

• To investigate age-related changes in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene expression in the human lung.
• To determine if reduced CFTR expression contributes to the age-associated decline in MC.

Main Methods:

• Utilized bulk (GTEx) and single-cell (CELLxGENE) lung sequencing data.
• Analyzed CFTR expression patterns across different lung cell types in relation to age.

Main Results:

• Both bulk and single-cell analyses revealed a significant decrease in CFTR expression with increasing age.
• CFTR expression declined in goblet, club, and basal cells, which are major sources of CFTR.
• No significant age-related decrease in CFTR expression was observed in ciliated airway cells.

Conclusions:

• Decreased CFTR expression in aging lung secretory and basal cells may lead to ASL dehydration.
• This dehydration can impair MC, contributing to the higher susceptibility to lung infections in the elderly.
• Findings highlight a potential molecular mechanism underlying age-related pulmonary defense deficits.